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Symptom Improvement Following Treatment with the Inhaled Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine in Patients with Moderate to Severe COPD – A Detailed Analysis

Authors Watz H, Rickard K, Rheault T, Bengtsson T, Singh D

Received 29 May 2020

Accepted for publication 20 August 2020

Published 16 September 2020 Volume 2020:15 Pages 2199—2206


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell

Henrik Watz,1 Kathleen Rickard,2 Tara Rheault,2 Thomas Bengtsson,3 Dave Singh4

1Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 2Verona Pharma Plc, Raleigh, NC, USA; 3StatMind AB, Lund, Sweden; 4Medicines Evaluation Unit, University of Manchester & Manchester University NHS Foundation Trust, Manchester, UK

Correspondence: Henrik Watz
Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Centre North (ARCN), German Centre for Lung Research (DZL), Wöhrendamm 80, Grosshansdorf 22927, Germany
Tel +49-4102-8881-0
Fax +49-4102-8881-114

Introduction: Ensifentrine is an inhaled first-in-class dual inhibitor of phosphodiesterase (PDE) 3 and 4. In a four-week randomized, double-blind, placebo-controlled, parallel-group study in patients with chronic obstructive pulmonary disease (COPD), nebulized ensifentrine 0.75 to 6mg twice daily significantly improved bronchodilation and symptoms, with all doses being well tolerated. Here, we report data for a number of prespecified exploratory and post hoc endpoints from this study that help to further profile the effect of ensifentrine on symptoms.
Methods: Eligible patients were males or females aged 40– 75 years with COPD, post-bronchodilator forced expiratory volume in 1 second 40– 80% predicted. Other than being clinically stable for at least four weeks prior to entry, there were no symptomatic inclusion or exclusion criteria. The outcome measures reported in this manuscript are the Evaluating Respiratory Symptoms [E-RS™:COPD] questionnaire total score and subscales (breathlessness, cough/sputum and chest symptoms) at Weeks 1– 4, Transition Dyspnea Index (TDI) focal score at Weeks 2 and 4, and St George’s Respiratory Questionnaire – COPD Specific (SGRQ-C) total score and domain data (symptoms, activity and impacts) at Week 4.
Results: There was a gradual improvement versus placebo with all ensifentrine doses for all three E-RS™:COPD subscales from Week 1 to Week 4, with the greatest ensifentrine effect on the breathlessness subscale, and all four doses superior to placebo from Week 2 onwards (p< 0.05). For TDI focal score, all ensifentrine doses were superior to placebo at Weeks 2 and 4 (p< 0.05). In the individual SGRQ-C domains at Week 4, ensifentrine had the greatest effect on the symptoms domain, with ensifentrine 6mg superior to placebo (p< 0.05).
Conclusion: In these analyses, ensifentrine demonstrated a notable early and meaningful effect on dyspnea, with this effect observed across two different assessment tools.

Keywords: phosphodiesterase inhibitors, chronic obstructive pulmonary disease, signs and symptoms, respiratory, drug therapy

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